Chimeric antigen receptor (CAR)-modified T cells have demonstrated remarkable efficacy in treating
B-cell leukemia. However, treated patients may potentially develop side effects, such as
cytokine release syndrome (CRS), the mechanisms of which remain unclear. Here, we collected 43 serum samples from eight patients with B-cell
acute lymphoblastic leukemia (B-ALL) before and five time points after CD19-specific CAR-T cell treatment. Using TMTpro 16-plex-based quantitative proteomics, we quantified 1151
proteins and profiled the longitudinal
proteomes analysis of each patient. Seven days after
therapy, we found the most dysregulated inflammatory
proteins. Lipid metabolism
proteins, including APOA1, decreased after
therapy, reached their minimum after 7 days, and then gradually recovered. Hence, APOA1 has been selected as a potential
biomarker of the CRS
disease progression. Furthermore, we identified CD163 as a potential
biomarker of CRS severity. These two
biomarkers were successfully validated using targeted proteomics in an independent cohort. Our study provides new insights into CAR-T cell therapy-induced CRS. The
biomarkers we identified may help develop targeted drugs and monitoring strategies.